Growth hormone (GH) secretion is regulated by two hypothalamic peptides: somatostatin, which inhibits GH release; and growth hormone-releasing factor (GRF), which stimulates the synthesis and release of GH. We are using GRF as a tool to study the neuroendocrine regulation of FH, and exploring the potential uses of GRF in the diagnosis and treatment of diseases including GH deficiency (dwarfism) and GH excess (gigantism and acromegaly). During the past year we have determined the dose-response curve for the stimulation of GH by GRF (1-44) NH2 (GRF-44) in normal men and women, and on this basis have developed a standardized GRF test. We have tested children in various developmental stages and aging adults to provide a normal range throughout life. Using the GRF test, we have studied patients with acromegaly to determine what proportion respond to GRF, and whether the response could be used to assess their clinical status. The majority responded to GRF with a prompt rise in GH. Most responses overlapped with the normal range, and the response did not correlate with clinical or biochemical features of the disease. We have compared the responses of GH deficient (GHD) children with those of age-matched normal control children. The majority (80%) of children with GHD have measurable GH responses to GRF: they are lower as a group than those of controls, but overlap with the normal range. This indicates that GHD is usually due to GRF deficiency, and that GRF might therefore be used as a therapy for GHD. To test this possibility, we have administered GRF or placebo repeatedly to 9 children with GHD. In 6 of the 9, each dose of GRF stimulated and burst of GH secretion. Over the course of treatment plasma somatomedin-C rose toward normal, and linear growth rates were accelerated to a degree comparable to or greater than that of standard doses of hGH. Thus it appears that GRF could become an alternative therapy of GHD in the majority of cases.